BackgroundIntrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos.MethodsChick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20) and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF) and its scavenger soluble VEGF receptor-1 (sFlt-1) to investigate the potential role of this hypoxia-regulated cytokine.Principal FindingsGrowth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV) dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype.Conclusions/SignificanceOur data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood.

Abstract-We compared the effect n-3 polyunsaturated fatty acids (PUFAs) with direct renin inhibition on electrophysiological remodeling in angiotensin II-induced cardiac injury. We treated double-transgenic rats expressing the human renin and angiotensinogen genes (dTGRs) from week 4 to 7 with n-3 PUFA ethyl-esters (Omacor; 25-g/kg diet) or a direct renin inhibitor (aliskiren; 3 mg/kg per day). Sprague-Dawley rats were controls. We performed electrocardiographic, magnetocardiographic, and programmed electrical stimulation. Dietary n-3 PUFAs increased the cardiac content of eicosapentaenoic and docosahexaenoic acid. At week 7, mortality in dTGRs was 31%, whereas none of the n-3 PUFA-or aliskiren-treated dTGRs died. Systolic blood pressure was modestly reduced in n-3 PUFA-treated (180Ϯ3 mm Hg) compared with dTGRs (208Ϯ5 mm Hg). Aliskiren-treated dTGRs and SpragueDawley rats were normotensive (110Ϯ3 and 119Ϯ6 mm Hg, respectively). Both n-3 PUFA-treated and untreated dTGRs showed cardiac hypertrophy and increased atrial natriuretic peptide levels. Prolonged QRS and QT c intervals and increased T-wave dispersion in dTGRs were reduced by n-3 PUFAs or aliskiren. Both treatments reduced arrhythmia induction from 75% in dTGRs to 17% versus 0% in Sprague-Dawley rats. Macrophage infiltration and fibrosis were reduced by n-3 PUFAs and aliskiren. Connexin 43, a mediator of intermyocyte conduction, was redistributed to the lateral cell membranes in dTGRs. n-3 PUFAs and aliskiren restored normal localization to the intercalated disks. Thus, n-3 PUFAs and aliskiren improved electrical remodeling, arrhythmia induction, and connexin 43 expression, despite a 70-mm Hg difference in blood pressure and the development of cardiac hypertrophy. Key Words: angiotensin II Ⅲ renin inhibition Ⅲ n-3 PUFA Ⅲ arrhythmias Ⅲ magnetocardiography H ypertensive heart disease causes heart failure and arrhythmia propensity. Ischemia, cardiac hypertrophy, fibrosis, inflammation, and electrical remodeling all contribute to the pathogenesis. 1,2 The renin-angiotensin-aldosterone system is a primary driver, and its blockade is state-of-the-art therapy. We provided initial evidence that direct renin inhibition (DRI) in transgenic rats harboring the human renin and angiotensinogen genes (dTGRs) improves target organ damage. 3-5 Untreated dTGRs developed severe hypertension, hypertrophy, inflammation, fibrosis, and small myocardial infarctions. Ventricular arrhythmias and, consequently, sudden cardiac death contributed to the high mortality rate at the early age of 7 weeks. 6 Electrical remodeling in dTGRs included dysregulation of the I to potassium channel, Ca 2ϩ -cycling proteins, and connexin (Cx) 43 gap junctions. 6,7 n-3 polyunsaturated fatty acids (PUFAs), contained in marine fish oil, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lead to cardioprotection and reduce sudden cardiac death. 8 The molecular mechanisms by which n-3 PUFAs exert their cardioprotective effects are not fully understood. n-3 PUFAs putatively affect membran...

The studied ICD lead with a floating atrial sensing dipole met the predefined safety expectation and demonstrated appropriate atrial sensing performance.

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The MACPAF study revealed a superiority of the Arctic Front® catheter concerning complete PVI. Owing to the insufficient efficacy of the HD Mesh Ablator® catheter, the safety board decided to stop MACPAF prematurely.